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RNAi Draws a Crowd to Waltham: Optimism Abounds

Several words in this article have been changed from a previous version, to more clearly and accurately describe the mechanism through which RNAi acts in the cell.


WALTHAM, Mass, May 6 - Layoffs? Downturn? What are you talking about? At the RNAi 2003 conference taking place this week at the Doubletree Guest Suites in Waltham, Mass., it might as well be 1999.


Nearly 200 people have shown up for this one-track, two-day event off I-95, which was organized not by a major conference company but by a former PerkinElmer scientist, Krishnarao Appasani.


In his welcoming address to a packed room, Appasani pointed to the surge in publications related to RNAi: A PubMed search for 1998 shows there were only 11 papers on RNAi, whereas in 2002 the number had jumped to 421. Appasani has recently launched the company GeneExpression Systems, not only to organize meetings like this one, but also to perform lab services such as immunohistochemistry, microarray hybridizations, and eventually, RNAi.


"People anticipate that the whole pipeline is going to be reduced in drug development" because RNAi will speed up target validation so much, he told GenomeWeb. But as with any new technology in the life sciences field, it's not always apparent whether this promise will be borne out by results. "Is it hype or is it reality?" Appasani asked.


The day's talks veered toward a consensus that there is real promise that this technology -- in which double-stranded RNA introduced into the nucleus of the cell triggers a pathway of interference with translation of RNA messages -- will deliver on its promise.


"The advantage of RNAi is that it will be a simple method compared to the others," said opening speaker Arthur Pardee, a professor Emeritus at HarvardMedicalSchool.


At 83, Pardee has plunged into the RNAi waters as excitedly as younger scientists, putting his postdoc to work on transfecting lines of breast cancer cells with siRNAs to see if they can learn more about the gene function in these cells.


But he has been around long enough to recognize that this new technology is not going to be the magic eight-ball for answering all biological questions. "I predict there are going to be problems," he said. These technologies, "are always not as easy as you think" they're going to be.


Several talks discussed the use of RNAi and green fluorescent proteins in C. elegans to map out this organism's deceptively complex cellular circuitry. As in the genome sequencing era, this organism has become a testing ground for various RNAi methods, and one where technological hurdles have been crossed first. "Intracellular delivery of siRNA is a challenge," said Craig Hunter, of Harvard. But this problem has been "solved in C. elegans. It doesn't matter whether you inject siRNA, or soak the organisms in [double-stranded] RNA solution, or feed them bacteria with siRNA."


This simple success has not yet jumped into the mammalian realm, and the issue of how to best package and deliver RNAi -- in particular the 21-25 base-pair short interfering RNA that works to trigger inhibition of RNA translation in mammals -- was a major topic in remaining talks. While some have focused on introducing chemically synthesized siRNA into cell lines, adenoviral and retroviral vectors, as well as DNA cassettes, are also being explored as mechanisms for delivering siRNA into the cell. Delivery, said Appasani, "is a big issue in the whole field of antisense and RNAi."


But Ken Reed, director of research and technology for Benitec in Australia, expressed optimism that the problem of delivery and other technical glitches would soon be solved. "We know what can be done. We may not know how to do it. But soon we will," he said.

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